Elaine W. Raines

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University of Washington
School of Medicine
Pathology
Research ProfessorAppointed: 1991

Mailing Address

Harborview Medical Center
Department of Pathology
Box 359675
Seattle, Washington 98104-2499
United States

Contact Information

Phone: (206) 341-5410
Fax: (206) 341-5416
ewraines@u.washington.edu

Qualifications

M.S., University of California Medical Center, Biochemistry, 1975.

Expertise and Research Interests

Lesions of atherosclerosis are the consequence of focal accumulation within the arterial intima of inflammatory cells from the circulation and smooth muscle (SMC) from the underlying media. Our laboratory has been examining the cellular and molecular mechanisms involved in this process, with a particular focus on the platelet-derived growth factor (PDGF), a potent stimulant of SMC migration and proliferation. Current questions include:

How does SMC interaction with specific matrix components alter its ability to respond to PDGF? Our working hypothesis is that the extracellular matrix within the normal artery may be nonpermisssive for SMC proliferation and migration.

What is the role of a novel metalloproteinase-like, disintegrin-like, cysteine-rich protein (MCD15) in vascular cells? For SMC to migrate from the media into the intima, they must alter their interactions with the surrounding matrix.

We have cloned a novel gene, MDC15, which is a potential regulator of matrix interactions and matrixdegradation. MDC15 is not expressed in normal vessels, but it is upregulated in lesions of atherosclerosis.

What are the signaling pathways responsible for stimulation of PDGF-induced migration? We have identified distinct signaling pathways associated with PDGF stimulation of SMC migration, and have established the requirement for actin polymerization and focal adhesion formation for migration to proceed.

What is the role of PDGF in vivo? Within developing lesionsof atherosclerosis, the primary sources of PDGF appears to be macrophages and platelets. By developing chimeric mice in which circulating cells are replaced with fetal liver cells from PDGF -/- mice, we are testing the role of PDGF in the formation oflesions of atherosclerosis and other fibrotic responses.

What is the role of macrophage turnover and activation in the development of lesions of atherosclerosis? Overamplification of the macrophage defensive role may contribute to lesion expansion. We are testing this hypothesis by evaluating the role of bcl-2 family members in monocyte apoptosis and secondary activation of macrophage genes such as PDGF in culture and in developing lesions of atherosclerosis in Apo E mice.

Keywords

COS Keywords:

Cardiovascular Biology, Cardiovascular System, Cell Biology, Embryology, Gene Expression, Gene Regulation, Growth Factor Receptors, Growth Factors, Immunobiology, Immunology, Lipid Metabolism, Lipoproteins, Nephrology, Receptors, Transplantation Immunology.

Additional Terms:

Cardiovascular Biology, Cell Biology, Embryology, Gene, Gene Expression, Gene Regulation, Growth Factor Receptors, Growth Factors, Immunobiology, Immunology, Lipid Metabolism, Lipoproteins, Nephrology, Tract Biology, Transplantation Biology, Urinary Biology.

Publications

  • Herren B, Levkau B, Raines E W, Ross R, Cleavage of beta-catenin and plakoglobin and shedding of VE-cadherin during endothelial apoptosis: evidence for a role for caspases and metalloproteinases., Molecular Biology of The Cell, 9(6), 1589-601, June 1998 Abstract
  • Nakashima Y, Raines E W, Plump A S, Breslow J L, Ross R, Upregulation of VCAM-1 and ICAM-1 at atherosclerosis-prone sites on the endothelium in the ApoE-deficient mouse., Arteriosclerosis, Thrombosis, and Vascular Biology, 18(5), 842-51, May 1998 Abstract
  • Levkau B, Koyama H, Raines E W, Clurman B E, Herren B, Orth K, Roberts J M, Ross R, Cleavage of p21Cip1/Waf1 and p27Kip1 mediates apoptosis in endothelial cells through activation of Cdk2: role of a caspase cascade., Molec. Cell, 1(4), 553-63, March 1998 Abstract
  • Levkau B, Herren B, Koyama H, Ross R, Raines E W, Caspase-mediated cleavage of focal adhesion kinase pp125FAK and disassembly of focal adhesions in human endothelial cell apoptosis., Journal of Experimental Medicine, 187(4), 579-86, 16 Feb 1998 Abstract
  • Evanko S P, Raines E W, Ross R, Gold L I, Wight T N, Proteoglycan distribution in lesions of atherosclerosis depends on lesion severity, structural characteristics, and the proximity of platelet-derived growth factor and transforming growth factor-beta., American Journal of Pathology, 152(2), 533-46, February 1998 Abstract
  • Bornfeldt K E, Campbell J S, Koyama H, Argast G M, Leslie C C, Raines E W, Krebs E G, Ross R, The mitogen-activated protein kinase pathway can mediate growth inhibition and proliferation in smooth muscle cells. Dependence on the availability of downstream targets., Journal of Clinical Investigation, 100(4), 875-85, 15 Aug 1997 Abstract
  • Herren B, Raines E W, Ross R, Three putative integrin ligands identified in human aortic smooth muscle cells., Annals of The New York Academy of Sciences, 811, 498-505, 15 Apr 1997 Abstract
  • Kaneko E, Yuan C, Skinner M P, Raines E W, Ross R, Serial magnetic resonance imaging of experimental atherosclerosis allows visualization of lesion characteristics and lesion progression in vivo., Annals of The New York Academy of Sciences, 811, 245-52; discussion 2, 15 Apr 1997 Abstract
  • Raines E W, Ross R, Is overamplification of the normal macrophage defensive role critical to lesion development?, Annals of The New York Academy of Sciences, 811, 76-85; discussion 85, 15 Apr 1997 Abstract
  • Herren B, Raines E W, Ross R, Expression of a disintegrin-like protein in cultured human vascular cells and in vivo., Faseb Journal, 11(2), 173-80, February 1997 Abstract
  • Koyama H, Raines E W, Bornfeldt K E, Roberts J M, Ross R, Fibrillar collagen inhibits arterial smooth muscle proliferation through regulation of Cdk2 inhibitors., Cell, 87(6), 1069-78, 13 Dec 1996 Abstract
  • Raines E W, Ross R, Multiple growth factors are associated with lesions of atherosclerosis: specificity or redundancy?, Bioessays, 18(4), 271-82, April 1996 Abstract
  • Graves L M, Bornfeldt K E, Sidhu J S, Argast G M, Raines E W, Ross R, Leslie C C, Krebs E G, Platelet-derived growth factor stimulates protein kinase A through a mitogen-activated protein kinase-dependent pathway in human arterial smooth muscle cells., Journal of Biological Chemistry, 271(1), 505-11, 5 Jan 1996 Abstract
  • Yuan C, Skinner M P, Kaneko E, Mitsumori L M, Hayes C E, Raines E W, Nelson J A, Ross R, Magnetic resonance imaging to study lesions of atherosclerosis in the hyperlipidemic rabbit aorta., Magnetic Resonance Imaging, 14(1), 93-102, 1996 Abstract
  • Chang M Y, Sasahara M, Chait A, Raines E W, Ross R, Inhibition of hypercholesterolemia-induced atherosclerosis in the nonhuman primate by probucol. II. Cellular composition and proliferation., Arteriosclerosis, Thrombosis, and Vascular Biology, 15(10), 1631-40, October 1995 Abstract
  • Bornfeldt K E, Raines E W, Graves L M, Skinner M P, Krebs E G, Ross R, Platelet-derived growth factor. Distinct signal transduction pathways associated with migration versus proliferation., Annals of The New York Academy of Sciences, 766, 416-30, 7 Sep 1995 Abstract
  • Bornfeldt K E, Graves L M, Raines E W, Igarashi Y, Wayman G, Yamamura S, Yatomi Y, Sidhu J S, Krebs E G, Hakomori S, et al, Sphingosine-1-phosphate inhibits PDGF-induced chemotaxis of human arterial smooth muscle cells: spatial and temporal modulation of PDGF chemotactic signal transduction., Journal of Cell Biology, 130(1), 193-206, July 1995 Abstract
  • Battegay E J, Raines E W, Colbert T, Ross R, TNF-alpha stimulation of fibroblast proliferation. Dependence on platelet-derived growth factor (PDGF) secretion and alteration of PDGF receptor expression., Journal of Immunology, 154(11), 6040-7, 1 Jun 1995 Abstract
  • Raines E W, Ross R, Biology of atherosclerotic plaque formation: possible role of growth factors in lesion development and the potential impact of soy., Journal of Nutrition, 125(3 Suppl), 624S-630S, March 1995 Abstract
  • Liaw L, Skinner M P, Raines E W, Ross R, Cheresh D A, Schwartz S M, Giachelli C M, The adhesive and migratory effects of osteopontin are mediated via distinct cell surface integrins. Role of alpha v beta 3 in smooth muscle cell migration to osteopontin in vitro., Journal of Clinical Investigation, 95(2), 713-24, February 1995 Abstract
  • Skinner M P, Yuan C, Mitsumori L, Hayes C E, Raines E W, Nelson J A, Ross R, Serial magnetic resonance imaging of experimental atherosclerosis detects lesion fine structure, progression and complications in vivo [see comments] [published erratum appears in Nat Med 1995 Mar;1(3, Nature Medicine, 1(1), 69-73, January 1995 Abstract
  • Skinner M P, Raines E W, Ross R, Dynamic expression of alpha 1 beta 1 and alpha 2 beta 1 integrin receptors by human vascular smooth muscle cells. Alpha 2 beta 1 integrin is required for chemotaxis across type I collagen-coated membr, American Journal of Pathology, 145(5), 1070-81, November 1994 Abstract
  • Sasahara M, Raines E W, Chait A, Carew T E, Steinberg D, Wahl P W, Ross R, Inhibition of hypercholesterolemia-induced atherosclerosis in the nonhuman primate by probucol. I. Is the extent of atherosclerosis related to resistance of LDL to oxidation?, Journal of Clinical Investigation, 94(1), 155-64, July 1994 Abstract
  • Kott J N, Westrum L E, Raines E W, Sasahara M, Ross R, Olfactory ensheathing glia and platelet-derived growth factor B-chain reactivity in the transplanted rat olfactory bulb., International Journal of Developmental Neuroscience, 12(4), 315-23, June 1994 Abstract
  • Seifert R A, Coats S A, Raines E W, Ross R, Bowen-Pope D F, Platelet-derived growth factor (PDGF) receptor alpha-subunit mutant and reconstituted cell lines demonstrate that transforming growth factor-beta can be mitogenic through PDGF A-chain-dependent and -i, Journal of Biological Chemistry, 269(19), 13951-5, 13 May 1994 Abstract
  • Bornfeldt K E, Raines E W, Nakano T, Graves L M, Krebs E G, Ross R, Insulin-like growth factor-I and platelet-derived growth factor-BB induce directed migration of human arterial smooth muscle cells via signaling pathways that are distinct from those of proliferation., Journal of Clinical Investigation, 93(3), 1266-74, March 1994 Abstract
  • Nakano T, Raines E W, Abraham J A, Klagsbrun M, Ross R, Lysophosphatidylcholine upregulates the level of heparin-binding epidermal growth factor-like growth factor mRNA in human monocytes., Proceedings of the National Academy of Sciences (USA), 91(3), 1069-73, 1 Feb 1994 Abstract
  • Nakashima Y, Plump A S, Raines E W, Breslow J L, Ross R, ApoE-deficient mice develop lesions of all phases of atherosclerosis throughout the arterial tree., Arteriosclerosis and Thrombosis, 14(1), 133-40, January 1994 Abstract
  • Tsai L H, White L, Raines E, Ross R, Smith R G, Cushley W, Ozanne B, Expression of platelet-derived growth factor and its receptors by two pre-B acute lymphocytic leukemia cell lines., Blood, 83(1), 51-5, 1 Jan 1994 Abstract
  • Yonemura K, Raines E W, Ahn N G, Narayanan A S, Mitogenic signaling mechanisms of human cementum-derived growth factors., Journal of Biological Chemistry, 268(35), 26120-6, 15 Dec 1993 Abstract
  • Graves L M, Bornfeldt K E, Raines E W, Potts B C, Macdonald S G, Ross R, Krebs E G, Protein kinase A antagonizes platelet-derived growth factor-induced signaling by mitogen-activated protein kinase in human arterial smooth muscle cells., Proceedings of the National Academy of Sciences (USA), 90(21), 10300-4, 1 Nov 1993 Abstract
  • Nakano T, Raines E W, Abraham J A, Wenzel F G 4th, Higashiyama S, Klagsbrun M, Ross R, Glucocorticoid inhibits thrombin-induced expression of platelet-derived growth factor A-chain and heparin-binding epidermal growth factor-like growth factor in human aortic smooth muscle cells., Journal of Biological Chemistry, 268(30), 22941-7, 25 Oct 1993 Abstract
  • Jackson C L, Raines E W, Ross R, Reidy M A, Role of endogenous platelet-derived growth factor in arterial smooth muscle cell migration after balloon catheter injury., Arteriosclerosis and Thrombosis, 13(8), 1218-26, August 1993 Abstract
  • Kraiss L W, Raines E W, Wilcox J N, Seifert R A, Barrett T B, Kirkman T R, Hart C E, Bowen-Pope D F, Ross R, Clowes A W, Regional expression of the platelet-derived growth factor and its receptors in a primate graft model of vessel wall assembly., Journal of Clinical Investigation, 92(1), 338-48, July 1993 Abstract
  • Raines E W, Ross R, Smooth muscle cells and the pathogenesis of the lesions of atherosclerosis., British Heart Journal, 69(1 Suppl), S30-7, January 1993 Abstract
  • Sasahara A, Kott J N, Sasahara M, Raines E W, Ross R, Westrum L E, Platelet-derived growth factor B-chain-like immunoreactivity in the developing and adult rat brain., Brain research. Developmental Brain Research, 68(1), 41-53, 24 Jul 1992 Abstract
  • Johnson R J, Raines E W, Floege J, Yoshimura A, Pritzl P, Alpers C, Ross R, Inhibition of mesangial cell proliferation and matrix expansion in glomerulonephritis in the rat by antibody to platelet-derived growth factor., Journal of Experimental Medicine, 175(5), 1413-6, 1 May 1992 Abstract
  • Raines E W, Lane T F, Iruela-Arispe M L, Ross R, Sage E H, The extracellular glycoprotein SPARC interacts with platelet-derived growth factor (PDGF)-AB and -BB and inhibits the binding of PDGF to its receptors., Proceedings of the National Academy of Sciences (USA), 89(4), 1281-5, 15 Feb 1992 Abstract
  • Raines E W, Ross R, Compartmentalization of PDGF on extracellular binding sites dependent on exon-6-encoded sequences., Journal of Cell Biology, 116(2), 533-43, January 1992 Abstract
  • Ferns G A, Raines E W, Sprugel K H, Motani A S, Reidy M A, Ross R, Inhibition of neointimal smooth muscle accumulation after angioplasty by an antibody to PDGF., Science, 253(5024), 1129-32, 6 Sep 1991 Abstract
  • Malden L T, Chait A, Raines E W, Ross R, The influence of oxidatively modified low density lipoproteins on expression of platelet-derived growth factor by human monocyte-derived macrophages., Journal of Biological Chemistry, 266(21), 13901-7, 25 Jul 1991 Abstract
  • Nakae H, Narayanan A S, Raines E, Page R C, Isolation and partial characterization of mitogenic factors from cementum., Biochemistry, 30(29), 7047-52, 23 Jul 1991 Abstract
  • Madtes D K, Malden L T, Raines E W, Ross R, Induction of transcription and secretion of TGF-alpha by activated human monocytes., Chest, 99(3 Suppl), 79S, March 1991 Abstract
  • Golden M A, Au Y P, Kirkman T R, Wilcox J N, Raines E W, Ross R, Clowes A W, Platelet-derived growth factor activity and mRNA expression in healing vascular grafts in baboons. Association in vivo of platelet-derived growth factor mRNA and protein with cellular proliferation., Journal of Clinical Investigation, 87(2), 406-14, February 1991 Abstract
  • Sasahara M, Fries J W, Raines E W, Gown A M, Westrum L E, Frosch M P, Bonthron D T, Ross R, Collins T, PDGF B-chain in neurons of the central nervous system, posterior pituitary, and in a transgenic model., Cell, 64(1), 217-27, 11 Jan 1991 Abstract
  • Battegay E J, Raines E W, Seifert R A, Bowen-Pope D F, Ross R, TGF-beta induces bimodal proliferation of connective tissue cells via complex control of an autocrine PDGF loop., Cell, 63(3), 515-24, 2 Nov 1990 Abstract
  • Dower S K, Qwarnstrom E E, Page R C, Blanton R A, Kupper T S, Raines E, Ross R, Sims J E, Biology of the interleukin-1 receptor., Journal of Investigative Dermatology, 94(6 Suppl), 68S-73S, June 1990 Abstract
  • Ross R, Masuda J, Raines E W, Gown A M, Katsuda S, Sasahara M, Malden L T, Masuko H, Sato H, Localization of PDGF-B protein in macrophages in all phases of atherogenesis., Science, 248(4958), 1009-12, 25 May 1990 Abstract
  • Ross R, Bowen-Pope D F, Raines E W, Platelet-derived growth factor and its role in health and disease., Philosophical Transactions of The Royal Society of london. Series B: Biological Sciences, 327(1239), 155-69, 12 Mar 1990 Abstract
  • Hart C E, Bailey M, Curtis D A, Osborn S, Raines E, Ross R, Forstrom J W, Purification of PDGF-AB and PDGF-BB from human platelet extracts and identification of all three PDGF dimers in human platelets., Biochemistry, 29(1), 166-72, 9 Jan 1990 Abstract
  • Ross R, Masuda J, Raines E W, Cellular interactions, growth factors, and smooth muscle proliferation in atherogenesis., Annals of The New York Academy of Sciences, 598, 102-12, 1990 Abstract
  • Ferns G A, Sprugel K H, Seifert R A, Bowen-Pope D F, Kelly J D, Murray M, Raines E W, Ross R, Relative platelet-derived growth factor receptor subunit expression determines cell migration to different dimeric forms of PDGF., Growth Factors, 3(4), 315-24, 1990 Abstract
  • Sakariassen K S, Powell J S, Raines E W, Ross R, Selective expression of mRNA encoding platelet-derived growth factor B chain following transfection of foreign genes into cell lines derived from baby hamster kidney., Journal of Cellular Biochemistry, 39(1), 87-94, January 1989 Abstract

Profile Details

Last Updated: 9/19/2000

COS Expertise ID #307833
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